High glucose and endothelial cell growth: novel effects independent of autocrine TGF-beta 1 and hyperosmolarity

McGinn, S., Poronnik, P., King, M., Gallery, E. D. M. and Pollock, C. A. (2003) High glucose and endothelial cell growth: novel effects independent of autocrine TGF-beta 1 and hyperosmolarity. American Journal of Physiology-cell Physiology, 284 6: C1374-C1386. doi:10.1152/ajpcell.00466.2002


Author McGinn, S.
Poronnik, P.
King, M.
Gallery, E. D. M.
Pollock, C. A.
Title High glucose and endothelial cell growth: novel effects independent of autocrine TGF-beta 1 and hyperosmolarity
Journal name American Journal of Physiology-cell Physiology   Check publisher's open access policy
ISSN 0363-6143
Publication date 2003-01-01
Sub-type Article (original research)
DOI 10.1152/ajpcell.00466.2002
Open Access Status DOI
Volume 284
Issue 6
Start page C1374
End page C1386
Total pages 13
Place of publication Bethesda
Publisher Amer Physiological Soc
Language eng
Abstract Human endothelial cells were exposed to 5 mM glucose ( control), 25 mM ( high) glucose, or osmotic control for 72 h. TGF-beta1 production, cell growth, death, and cell cycle progression, and the effects of TGF-beta1 and TGF-beta neutralization on these parameters were studied. High glucose and hyperosmolarity increased endothelial TGF-beta1 secretion (P < 0.0001) and bioactivity (P < 0.0001). However, high glucose had a greater effect on reducing endothelial cell number ( P < 0.001) and increasing cellular protein content (P < 0.001) than the osmotic control. TGF-beta antibody only reversed the antiproliferative and hypertrophic effects of high glucose. High glucose altered cell cycle progression and cyclin-dependent kinase inhibitor expression independently of hyperosmolarity. High glucose increased endothelial cell apoptosis ( P < 0.01), whereas hyperosmolarity induced endothelial cell necrosis ( P < 0.001). TGF-beta antibody did not reverse the apoptotic effects observed with high glucose. Exogenous TGF-beta1 mimicked the increased S phase delay but not endoreduplication observed with high glucose. High glucose altered endothelial cell growth, apoptosis, and cell cycle progression. These growth effects occurred principally via a TGF-beta1 autocrine pathway. In contrast, apoptosis and endoreduplication occurred independently of this cytokine and hyperosmolarity.
Keyword Cell Biology
Physiology
endothelial cells
diabetes mellitus
apoptosis
endoreduplication
transforming growth factor-beta 1
Beta-inducible Gene-h3
Transforming Growth-factor-beta-1
Tgf-beta
Accelerated Death
Renal Hypertrophy
Elevated Glucose
Mesangial Cells
Proximal Tubule
Expression
Proliferation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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Created: Thu, 20 Sep 2007, 02:39:52 EST